I sat down with two outstanding ADDF-funded researchers recently to talk about the latest news on their cutting-edge work, the inspiration for their ideas, and when we can expect results from their latest trials. Frank Longo, M.D., Ph.D., chairman of neurology at Stanford University and chairman of the Board and Founder of PharmatrophiX and Kent Leslie, M.Sc., chief scientific officer of Amylyx Pharmaceuticals, joined me at a recent virtual panel discussion, which was part of our 11th Annual Great Ladies Luncheon.
Long-time Alzheimer’s researcher moved beyond amyloid
Dr. Longo is a long-time Alzheimer’s researcher. ADDF honored him with the inaugural Melvin R. Goodes Prize for Excellence in Alzheimer’s Drug Discovery in 2015 and his team’s work was featured on the cover of Time magazine the following year. Dr. Longo is a giant in our field.
Longo and his team are currently completing a phase 2a trial of their lead drug candidate in patients with mild to moderate Alzheimer’s disease. The compound, called C-31, affects a receptor on neurons called p75, helping to counteract processes that lead to abnormal signaling in the brain’s synapses and degeneration and death of the brain’s neurons.
While it is more common to hear about novel Alzheimer’s drug targets today, Dr. Longo reminded us that when he started work on C-31, it wasn’t common to look beyond amyloid. He wanted to go deeper than amyloid and the ADDF was there to support his ideas with both funding and intellectual support. Years later, the field broadly accepts that we need to go after a range of targets.
C-31 is a small molecule, which means it can be taken orally. The active drug crosses the brain-blood barrier where it attaches to neurons to modulate activity on their surface to counteract the degenerative processes triggered by amyloid and pathologic forms of tau. The goal is to makes neurons more resilient to degeneration and death.
The current phase 2a trial is an exploratory endpoints trial. No one has tested this kind of mechanism before, so the trial is designed to measure several outcomes to see where the drug has relevant activity. Armed with this information, the team hopes to design a phase 3 efficacy trial, the type of large-scale trial needed for FDA approval. They plan to present findings at an upcoming international medical meeting.
Repurposed drugs make up first-of-its kind combination Alzheimer’s therapy in clinical trials
In neurodegenerative diseases, it is rare to find a single genetic cause or culprit associated with the disease. Typically, multiple things are going awry simultaneously. This led some young scientists at Brown University, including chief scientific officer of Amylyx Pharmaceuticals Kent Leslie, to think, “we need to target several of them at the same time.”
That idea became Amylyx’s AMX0035 (sodium phenylbutyrate (PB)-taurursodiol (TURSO)), a combination of two repurposed drugs with distinct medical purposes and mechanisms of action designed to target two underlying cellular mechanisms associated with neurodegeneration. Combination therapies are a mainstay in HIV, cancer and heart disease treatment and they are sure to be a valuable tool for Alzheimer’s.
Because AMX0035 is composed of repurposed drugs that have already been tested and used extensively in patients, their research is moving faster than normal. The FDA approved the move of AMX0035 from a concept into a 95-patient phase 2 trial without the usual phase 1 safety trials in healthy volunteers first.
Results from the AMX0035 phase 2 trial are due soon. We’re just as excited as Kent and the Amylyx team to see what’s next for this potential breakthrough therapy. While he’s proud that AMX0035 is the first combination therapy in trials for Alzheimer’s disease, Kent says he hopes others will follow along soon to provide new hope and new options for people with Alzheimer’s and their families.
Kent said at our conference that it’s hard to imagine where we would be in Alzheimer’s research without the ADDF. In turn, we are proud to work with such amazing researchers like Kent Leslie and Frank Longo.
There is an accelerating ability to run clinical trials in a much better way than we could ever do before, particular in phase 2, where we learn a drug’s effects in patients. For me, that’s one of the most exciting things. All of the basic research and biomarker work has led to a new dawn in Alzheimer’ clinical trials. The future is bright.